If you have not already done so, you might try looking at the following
Dourson M.L. and J.F. Stara. 1983. Regulatory History and
Experimental Support of Uncertainty (Safety) Factors. Reg. Toxicol.
and Pharmacol. 3:224-238.
Barnes D.G. and M. Dourson. 1988. Reference Dose (RfD):
Description and Use in Health Risk Assessments. Regulatory
Toxicology and Pharmacology. 8:471-486.
Brown, S.L., S.M. Brett, M. Gough, J.V. Rodricks, R.G. Tardiff, and
D Turnbull. 1988. Review of Interspecies Risk Comparisons. Reg.
Toxicol. and Pharmacol. 8:191-206.
Johnson E.M. 1988. Cross-species Extrapolations and the Biologic
Basis for Safety Factor Determinations in Developmental Toxicology.
Reg. Toxicol. and Pharamacol. 8:22-36.
More recent papers may also be of interest to you in addressing this
question. Try a search of PubMed using "uncertainty, interspecies." To name
a few ...
Calabrese EJ, Baldwin LA. 1994. A Toxicological Basis to Derive a
Generic Interspecies Uncertainty Factor.Environ Health Perspect.
Carnes BA, Olshansky SJ, Grahn D. 1998. An interspecies
prediction of the risk of radiation-induced mortality. Radiat Res.
> We often use a 10-fold uncertainty factor when considering the
> intraspecies variability in reactions to a particular chemical. I am
> currently interested in looking at cases where that 10-fold factor may
> understate the true variability in the population. I would be greatly
> appreciative if somebody could either give me examples or point me in the
> direction of a good resource to find examples where this may be the case.
> Human variation in reactions to Prozac would be one example. Again, I'd
> appreciate any help that you could lend. Thank you very much!
James S. Smith, Jr., Ph.D.
President & Toxicologist
OAK CREEK, Inc.
Toxicology & Risk Assessment Consulting
RR 3 Box 246B
Gorham, Maine 04038-9428
Voice : 207.929.6375
E-mail : jssmith at oak-creek.net
WWW : http://www.oak-creek.net
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